Cardiovascular disease due to atherosclerosis remains the leading cause of death in the United States. Clinical symptoms and morbidity that result from atherosclerosis disease are due to plaque instability and are manifested as ulceration, thrombosis, and/or intraplaque hemorrhage. Much research has been directed at understanding atherogenesis, the progression of the disease and the final events that lead to heart attack or stroke. However, relatively little is known about how to identify "vulnerable" lesions in vivo noninvasively and to monitor the lesion progression longitudinally. This proposal presents a plan to measure the atherosclerotic plaque features quantitatively using lesion indices and to correlate the lesion indices to the development of clinical symptoms. We will focus our study on advanced lesions at the carotid bifurcation, due to 1) their close association to stroke, 2) their accessibility by high resolution MRI techniques, and 3) the accessibility of carotid samples due to carotid endarterectomy that provide us with an excellent opportunity to verify the MRI results by examining the samples histologically. The long term goal of this project is to identify characteristic magnetic resonance imaging markers for unstable vulnerable atherosclerotic plaque in the carotid artery. At present there are no reliable means to characterize these lesions in terms of features that are associated with vulnerable plaque in vivo. The specific aims are: 1) to develop/optimize lesion indices and 2) to test whether the size of lipid core, the thickness of the fibrous cap, and the extend of neovascularization (as expressed by MR lesion indices) can be associated with clinical symptoms. This project builds on studies that have been performed and that are on going in our laboratory. Improved methods of identifying high-risk plaques will result in better selection of patients for intervention. Development of an accurate, reproducible, and quantitative technique for directly assessing the status and progression of atherosclerotic lesions will significantly reduce the cost of clinical trials. Furthermore, the lesion indices will provide continuous parameter for tracking progression of the lesion rather than a categorical analysis provided by a lesion type evaluation. Lastly, prospective, serial high-resolution MRI of the developing carotid plaque will provide a unique opportunity to examine the processes involved in progression form a stable lesion to vulnerable plaque.